The present invention relates to an improved evaporation method for use with a mass spectrometer. More particularly, the present invention relates to high-power laser-induced acoustic desorption (LIAD) mass spectrometry probe designed to be coupled to a mass spectrometer for the subsequent ionization and analysis of non-volatile, thermally labile analytes.
The LIAD probe of the present invention improves the desorption efficiency of molecules having larger molecular weights through the use of higher laser irradiances. Energy from the laser pulses propagates through a metal foil or some other target, likely as an acoustic wave, resulting in desorption of neutral molecules from an opposite side of the foil into a mass spectrometer. As used herein, the term LIAD is intended to cover devices which supply energy from a laser to the back side of a target (such as a metal foil or other suitable target) having an analyte on the opposite side, regardless of whether or not an acoustic wave causes the desorption. Following desorption, the molecules are ionized by electron impact, chemical ionization or other suitable method. The mass spectrometer then measures the masses and relative concentrations of the ionized atoms and/or molecules.
Illustratively, the probe of the present invention increases the power density of the pulses applied to the metal foil compared to conventional LIAD probes. Illustratively, over a half of an order of magnitude greater power density (up to at least 5.0×109 W/cm2) is achievable on the backside of the foil with the high-power LIAD probe of the present invention compared to the conventional LIAD probes which have a maximum power density of 9.0×108 W/cm2.
According to an illustrated embodiment of the present invention, a laser-induced acoustic desorption (LIAD) probe is configured to desorb neutral molecules into a mass spectrometer. The probe includes a body portion having an interior region, a first end, and a second end configured to be inserted into a mass spectrometer. The probe also includes a window coupled to the second end of the body portion, a laser configured to generate a laser beam which passes into the first end of the body portion and through the window along a desorption axis, and a movable sample holder located adjacent the second end of the body portion spaced apart from the window. The movable sample holder is configured to receive a target having an analyte sample thereon and to move the target relative to the desorption axis so that different portions of the target and analyte sample thereon move into the path of the laser beam during a desorption process.
In one illustrated embodiment, a controller moves the sample holder in X and Y directions within a plane transverse to the desorption axis. In another illustrated embodiment, a controller rotates the sample holder about an axis of rotation spaced apart from the desorption axis.
According to another illustrated embodiment of the present invention, a method of desorbing a analyte sample into a mass spectrometer using laser-induced acoustic desorption (LIAD) comprises providing a LIAD probe to supply a laser beam along a desorption axis, providing a target having an analyte sample located thereon, positioning the target in the path of the laser beam, and providing relative movement between the desorption axis and the target so the different portions of the target and analyte sample are aligned with the desorption axis during a desorption process.
In an illustrated embodiment, the method further comprises ionizing neutral molecules desorbed from the analyte sample on the target after the desorption process.
In one illustrated embodiment, the step of providing relative movement between the desorption axis and the target includes rotating the target about an axis of rotation spaced apart from the desorption axis. In another illustrated embodiment, the step of providing relative movement between the desorption axis and the target includes rotating the LIAD probe relative to the target about an axis of rotation spaced apart from the desorption axis. In yet another illustrated embodiment, the step of providing relative movement between the desorption axis and the target includes moving the target in X and Y directions within a plane transverse to the desorption axis.
According to yet another illustrated embodiment of the present invention, a laser-induced acoustic desorption (LIAD) apparatus is configured to desorb neutral molecules into a mass spectrometer. The apparatus comprises a laser which generates a laser beam, and a probe including a body portion having an interior region, a first end, and a second end configured to be inserted into a mass spectrometer. The probe also includes a window coupled to the second end of the body portion and a target holder located adjacent the second end of the body portion spaced apart from the window. The body portion is positioned relative to the laser so that the laser beam enters the first end directly without the use of a fiber optic line, passes through the window, and strikes a target held by the target holder to desorb neutral molecules from an analyte sample on the target.
In one illustrated embodiment, the apparatus further comprises a frame coupled to the laser, an external focusing lens coupled to the frame, and at least one external mirror coupled to the frame. The at least one external mirror is aligned to reflect a laser beam emitted from the laser through an opening in the first end of the probe.
Also in an illustrated embodiment, the apparatus further comprises an internal focusing lens located in the interior region of the body portion, and first and second internal mirrors located within the interior region of the body portion. The first and second internal mirrors are positioned to reflect the laser beam entering the first end of the body portion to change an axis of the laser beam within the body portion from an entry axis to a spaced apart desorption axis, the desorption axis passing through the internal focusing lens, the window, and the target holder.
In one illustrated embodiment, the body portion includes an inner cylinder and an outer cylinder rotatable relative to the inner cylinder. The inner cylinder, the first and second internal mirrors, and the focusing lens are held in a fixed position. The outer cylinder and the target holder are rotatable about an axis of rotation spaced apart from the desorption axis to move the target relative to the desorption axis during a desorption process.
In another illustrated embodiment, the body portion includes an outer cylinder and an inner cylinder rotatable relative to the outer cylinder. The outer cylinder and the target holder are held in a fixed position. The inner cylinder, the first and second internal mirrors, and the focusing lens are rotatable about an axis of rotation spaced apart from the desorption axis to move the desorption axis relative to the target during a desorption process.
According to still another illustrated embodiment of the present invention, a method of desorbing a sample into a mass spectrometer using laser-induced acoustic desorption (LIAD) is provided. The method comprises providing a target having first and second sides, providing an analyte sample on the first side of the target, positioning the target adjacent a portion of the mass spectrometer, and desorbing neutral molecules from the analyte sample on the first side of the target using a high power LIAD probe to focus a laser beam along a desorption axis and generate a power density greater than 9×108 W/cm2 on the second side of the target.
In an illustrated embodiment, the method further comprises ionizing the neutral molecules after the desorbing step.
In a certain illustrated embodiment, the power density generated by the probe on the second side of the target is greater than 1.0×109 W/cm2. In another illustrated embodiment, the power density generated by the probe on the second side of the target is greater than 2.5×109 W/cm2. Preferably the power density generated by the probe on the second side of the target has a ranges from about 9×108 W/cm2 to about 5.0×109 W/cm2.
The probe generates a plurality of laser pulses on the second side of the target. In the illustrated embodiments, the pulses have an energy of greater than 4.5 mJ/pulse, greater than 6 mJ/pulse, and greater than 8 mJ/pulse. Preferably, the pulses having an energy range of about 4 mJ/pulse to about 13 mJ/pulse.
In certain illustrated embodiments, the analyte is a peptide having a molecular weight greater than 500 amu, greater than 750 amu, or greater than 1000 amu. In other illustrated embodiments, the analyte is a hydrocarbon polymer having a molecular weight greater than 1200 amu, greater than 1500 amu, or 1700 amu or greater.